A Phase III double-blind, randomised, placebo-controlled trial to evaluate liver-related clinical outcomes and safety of once weekly injected survodutide in participants with compensated nonalcoholic steatohepatitis/metabolic dysfunction associated steatohepatitis (NASH/MASH) cirrhosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,590
- 试验地点
- 16
- 主要终点
- Time to first occurrence of any component of the composite clinical endpoint (at EoS) consisting of: all-cause mortality, liver transplant, hepatic decompensation events, worsening of MELD score to greater than or equal to 15 and progression to CSPH
研究概览
简要总结
This study is open to adults who are at least 18 years old and have:
· A confirmed liver disease called non-alcoholic steatohepatitis (NASH) or
· A confirmed liver disease called metabolic-associated steatohepatitis (MASH)
· BMI of 27 kg/m2 or more or
· 25 kg/m2 or more if the participant is Asian.
People with a history of other chronic liver diseases or high alcohol intake cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people with NASH or MASH improve their liver function.
Participants are put into 2 groups randomly, which means by chance. 1 group gets survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Each participant has twice the chance of getting survodutide. Participants and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week. All participants regularly receive counselling to make changes to their diet and to exercise regularly.
Participants are in the study for up to 4 and a half years. During this time, they visit the study site or have a remote visit by video call every 2, 4 or 6 weeks for about a 1 year and 5 months. After this time participants visit the trial site or have a remote visit every 3 months until the end of the study.
The doctors check participants’ health and take note of any unwanted effects. The participants’ body weight is regularly measured. At some visits the liver parameters are measured using different imaging methods. The participants also fill in questionnaires about their symptoms. The results are compared between the groups to see whether the treatment works
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female adults Greater than or equal to 18 years of age at the time of screening, and at least the legal age of consent in countries where it is Greater than18 years
- •Body mass index (BMI) Greater than or equal to 27 kg/m2 (Greater than or equal to 25 kg/m2 for Asian trial participants)
- •Compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis diagnosed according to modified Liver Forum criteria
- •Magnetic resonance imaging proton density fat fraction (MRI-PDFF) fat fraction Greater than or equal to 5% or FibroScan with controlled attenuation parameter (CAP) Greater than or equal to 288 dB/m, obtained during the screening period or a historic MRI-PDFF or FibroScan with CAP Greater than or equal to 12 weeks prior to randomisation (except for patients with cryptogenic cirrhosis where MRI-PDFF Less than 5% or FibroScan with CAP less than 288 dB/m is allowed).
- •This inclusion criterion does not apply for participants with a recent (Greater than or equal to 12 months prior to randomisation) liver biopsy showing steatosis/steatohepatitis
- •Further inclusion criteria apply.
排除标准
- •Current or history (less than 5 years) of significant alcohol consumption, defined as an average of greater than140 g/week in female patients and greater than 210 g/week in male patients, for a period of greater than 3 consecutive months, or an inability to reliably quantify alcohol consumption based upon judgment of the investigator.
- •Model of end-stage liver Disease (MELD) score less than 12 due to liver disease
- •History or current (i.e. at screening) hepatic decompensation event of any of the following but not limited to a) History of portal hypertension-related upper gastrointestinal (GI) bleeding b) Ascites c) Hepatic encephalopathy (HE) greater than or equal to Grade 1 according to the West Haven criteria
- •Any of the following lab test result at screening a) Albumin below less than 3.5 g/dL (less than 35.0 g/L) b) International normalised ratio (INR) greater than 1.3 unless due to therapeutic anticoagulants c) Total bilirubin (TBL) greater than 1.2x upper limit of normal (ULN) NOTE: Trial participants with Gilbert Syndrome are eligible with a TBL greater than 1.2x ULN if reticulocyte count is within normal limits, haemoglobin is within normal limits unless due to chronic anaemia and unrelated to haemolysis, and direct bilirubin is less than 20% of TBL.
- •d) Alkaline phosphatase greater than 1.5x ULN e) Platelet count less than 100,000/µL (less than 100 GI/L)
- •History or evidence of other chronic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis or overlap syndrome, Wilsons disease, alpha-1-antitrypsin deficiency, or genetic haemochromatosis
- •Hepatitis B positive (defined as positive hepatitis B surface antigen (HBsAg))
- •Hepatitis C positive (defined as positive hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid (RNA))
- •Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 5x ULN
- •Evidence of alcoholic liver disease, or drug-induced liver disease, as defined on the basis of typical exposure and history
- •History of liver transplantation or listed for liver transplantation
- •History of transjugular intrahepatic portosystemic shunt (TIPS) or other radiological/surgical procedure for portal hypertension treatment
- •Further exclusion criteria apply.
结局指标
主要结局
Time to first occurrence of any component of the composite clinical endpoint (at EoS) consisting of: all-cause mortality, liver transplant, hepatic decompensation events, worsening of MELD score to greater than or equal to 15 and progression to CSPH
时间窗: up to 4.5 years
次要结局
- Absolute change from baseline in enhanced liver fibrosis (ELF) score(At baseline and at Week 76)
- Percentage change from baseline in body weight(At baseline and at Week 76)
- Absolute change from baseline in glycosylated haemoglobin A1c (HbA1c) in participants with type 2 diabetes mellitus (T2DM) at baseline (%)(At baseline and at Week 76)
- Absolute change from baseline in HbA1c in participants with T2DM at baseline (mmol/mol)(At baseline and at Week 76.)
- Absolute change from baseline in liver stiffness in FibroScan vibration-controlled transient elastography (VCTE) (kPa)(At baseline and at Week 76)
- Percentage change from baseline in liver stiffness in FibroScan VCTE(At baseline and at Week 76)
- Time to first occurrence of progression to CSPH(up to 4.5 years)
- Time to first occurrence of any of the hepatic decompensation events (ascites, HE, or portal hypertension-related upper GI bleeding), or worsening of MELD score to greater than or equal to 15(up to 4.5 years.)
- Occurrence of all-cause hospitalisation (first and recurrent)(up to 4.5 years)
- Time to first occurrence of any of the adjudicated components of the composite endpoint 5-point major adverse cardiac event (5P-MACE)(up to 4.5 years.)
- Absolute changes from baseline in lipids (mg/dL)(At baseline and at Week 76.)
- Absolute change from baseline in aspartate aminotransferase (AST) (U/L)(At baseline and at Week 76)
- Absolute change from baseline in alanine aminotransferase (ALT) (U/L)(At baseline and at Week 76)
- Absolute change from baseline in liver stiffness assesses by magnetic resonance elastography (MRE)(At baseline and at Week 76.)